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Abstract Title:

A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis.

Abstract Source:

J Neuroimmune Pharmacol. 2012 Dec ;7(4):1002-16. Epub 2012 Sep 14. PMID: 22971837

Abstract Author(s):

Aitor G Granja, Francisco Carrillo-Salinas, Alberto Pagani, María Gómez-Cañas, Roberto Negri, Carmen Navarrete, Miriam Mecha, Leyre Mestre, Bend L Fiebich, Irene Cantarero, Marco A Calzado, Maria L Bellido, Javier Fernandez-Ruiz, Giovanni Appendino, Carmen Guaza, Eduardo Muñoz

Article Affiliation:

Aitor G Granja

Abstract:

Phytocannabinoids like∆(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) show a beneficial effect on neuroinflammatory and neurodegenerative processes through cell membrane cannabinoid receptor (CBr)-dependent and -independent mechanisms. Natural and synthetic cannabinoids also target the nuclear receptor peroxisomeproliferator-activated receptor-gamma (PPARγ), an attractive molecular target for the treatment of neuroinflammation. As part of a study on the SAR of phytocannabinoids, we have investigated the effect of the oxidation modification in the resorcinol moiety of cannabigerol (CBG) on CB(1), CB(2) andPPARγ binding affinities, identifying cannabigerol quinone (VCE-003) as a potent anti-inflammatory agent. VCE-003 protected neuronal cells from excitotoxicity, activated PPARγ transcriptional activity and inhibited the release of pro-inflammatory mediators in LPS-stimulated microglial cells. Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis (MS) was used to investigate the anti-inflammatory activity of this compound in vivo. Motor function performance was evaluated and the neuroinflammatory response and gene expression pattern in brain and spinal cord were studiedby immunostaining and qRT-PCR. We found that VCE-003 ameliorated the symptoms associated to TMEV infection, decreased microglia reactivity and modulated the expression of genes involved in MS pathophysiology. These data lead us to consider VCE-003 to have high potential for drug development againstMS and perhaps other neuroinflammatory diseases.

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Sayer Ji
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